A nearly universal and important property of neuronal responses in the auditory pathway is adaptation to the stimulus, such that the neuronal responses to the same sound depend on the context in which the sound is presented. In central auditory pathway, neurons exhibit stimulus-specific adaptation (SSA), responding to the same tone more weakly when the tone is presented frequently, than when the tone is presented rarely. SSA is fundamentally different from adaptation found earlier in the auditory pathway, because it does not generalize across all inputs to a neuron, and therefore cannot be explained by a generalized reduction in excitability of the neuron. The mechanisms that give rise to SSA in the auditory pathway are not well understood. In specific aim 1, we test the hypothesis that two types of inhibitory interneurons facilitate SSA in the auditory cortex in a complementary fashion. In specific aim 2, we test the hypothesis that the auditory cortex provides SSA to the auditory midbrain. Understanding the mechanisms that give rise to SSA is important because SSA have been linked to detection of deviant sounds, a process that contributes to sound source separation and object grouping. However, a direct link between SSA and detection of deviant sounds has not been established. In specific aim 3, we test the hypothesis that SSA in the central auditory pathway facilitates detection of deviant sounds. Impact: Through innovative optogenetic, electrophysiological, and behavioral methods, the proposed research will (1) identify novel neuronal mechanisms that facilitate adaptation in the auditory pathway; (2) dissociate the functional roles of distinct cortical inhibitory circuits and cortico-collicular feedback in auditory processing; and (3) provide a direct test of these circuit elements in auditory perception.